Infection prevention and control measures in practices of the Swiss sentinel network during seasonal influenza epidemics.

BACKGROUND: There are limited data on the transmission of influenza in the context of primary care practices, despite the fact that a significant proportion of the population consult their primary care physician for an influenza-like illness every year. AIM: To describe the use of influenza prevention and control methods in private practices of the Swiss sentinel network. METHODS: This online cross-sectional survey collected data about infection prevention and control measures in the 166 private practices of the Swiss sentinel surveillance network during the 2018-2019 influenza season. Questions pertained to the practice setting, infection prevention and control recommendations, influenza vaccination status of the physicians and their staff, adhesion to hand hygiene, and mask wearing. FINDINGS: Among the 122 practices that answered (response rate 73.5%), 90.2% of the responding physicians had been vaccinated themselves, and 46.7% (56/120) estimated that their staff vaccination coverage was >60%, although it was offered to employees in all practices. Most practices (N=68, 55.7%) had no specific recommendations for their staff concerning mask wearing. Most physicians reported washing or disinfecting their hands before examining a patient (N=91, 74.6%), after examination (N=110, 90.2%) and before a medical procedure (N=112, 91.8%). However, this rate was lower for arrival at the practice (N=78, 63.9%) and leaving the practice (N=83, 68.0%). CONCLUSION: Most physicians in the Swiss sentinel surveillance network have been vaccinated themselves. However, the vaccination rates among their staff are low, despite vaccine availability. Hand hygiene measures were also suboptimal. These results warrant further efforts to implement infection prevention and control measures in the ambulatory setting.

[Buruli ulcers: an advocacy agenda to improve its control]. / Ulcère de Buruli : construction d'un agenda de plaidoyer pour améliorer la lutte.

Doctors Without Borders (Médecins Sans Frontières) has developed an advocacy agenda in Cameroon to better meet its patients' needs and to simplify control of Buruli ulcers. This agenda is based on 4 priorities: diagnostic (development of a clinical score), chemotherapeutic (to envision drug administration at home, without daily hospital visits), dressings, and HIV coinfection. These priority objectives should make it possible to reduce the duration of hospitalization and limit the need for surgery.

[Differential diagnoses of infection with Mycobacterium ulcerans: case reports from Akonolinga, Cameroon]. / Diagnostics différentiels de l'infection à Mycobacterium ulcerans : cas cliniques d'Akonolinga, Cameroun.

The authors describe the results of a program for the management of Buruli ulcers in Akonolinga (Cameroon). Its principal objective is to improve the diagnosis of dermatologic lesions and thereby to improve the indications for specific antibiotic therapy. This study, conducted in February, 2013, included 271 patients. Differential diagnosis of suspicious lesions was best with diagnostic examinations completed by histologic examination of a punch biopsy sample and advice from expert dermatologists.

Safety and effectiveness of amphotericin B deoxycholate for the treatment of visceral leishmaniasis in Uganda.

Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb(V)). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) = 2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI = 1.4%-7.9%) among the 161 patients treated with Sb(V) (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI = 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI = 0.1%-4.4%) of the patients treated with Sb(V) (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.

www.fevertravel.ch: an online study prototype to evaluate the safety and feasibility of computerized guidelines for fever in returning travellers and migrants.

Following the paper publication of practice guidelines for the management of febrile patients returning from the tropics, we constructed a consultation website that comprises a decision chart and specific diagnostic features providing medical diagnostic assistance to primary care physicians. We then integrated a research component to evaluate the implementation of these computerized guidelines. This study website has the same interface as the consultation website. In addition, one is able to record: (i) the pathway followed by the physician through the decision chart, (ii) the diagnostic tests performed, (iii) the initial and final diagnoses as well as outcome and (iv) reasons for non-adherence when the physician diverges from the proposed attitude. We believe that Internet technology is a powerful medium to reach physicians of different horizons in their own environment, and could prove to be an effective research tool to disseminate practice guidelines and evaluate their appropriateness. Here we describe the design, content, architecture and system implementation of this interactive study prototype aimed at integrating operational research in primary care practice.

Coagulase-negative staphylococci in very-low-birth-weight infants: inability of genetic markers to distinguish invasive strains from blood culture contaminants.

Selected coagulase-negative staphylococci from the blood of very-low-birth-weight infants in the Neonatal Intensive Care Unit at the Royal Women's Hospital, Melbourne, collected over a 5-year period were examined. Isolates were classified as invasive or contaminants, speciated, typed by pulsed-field gel electrophoresis, and examined for biofilm genes (icaA, icaC, and icaD), adhesion genes (atlE, fbe), and the number of copies of IS256. Of the 24 isolates studied, there were 13 contaminants and 11 invasive isolates. The collection included 15 Staphylococcus epidermidis, eight Staphylococcus capitis, and one each of Staphylococcus warneri and Staphylococcus haemolyticus. Two small clusters of S. epidermidis that belonged to the same molecular type were identified. All S. capitis isolates belonged to the same molecular type or subtype, suggesting that a particular clone was circulating in the unit. There was no significant difference in the species found, the presence of icaA, icaC, icaD, atlE, or fbe, or the number of copies of IS256 between invasive isolates and contaminants. A series of nasal isolates from nonhospitalized adults differed from hospital isolates in the absence of IS256 and the low prevalence of icaC. There was no evidence of IS256-mediated insertion into ica genes as a mechanism of phase variation. These findings suggest that contaminants and invasive isolates derived from the same pool of hospital strains capable of causing sepsis in compromised hosts and that other mechanisms of phase variation exist, apart from IS256 insertion into ica genes.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. We reviewed systematically data on smoking cessation rates from controlled trials that used biomedical risk assessment and feedback. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched he Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. MAIN RESULTS: From 4049 retrieved references, we selected 170 for full text assessment. We retained eight trials for data extraction and analysis. One of the eight used CO alone and CO + Genetic Susceptibility as two different intervention groups, giving rise to three possible comparisons. Three of the trials isolated the effect of exhaled CO on smoking cessation rates resulting in the following odds ratios (ORs) and 95% confidence intervals (95% CI): 0.73 (0.38 to 1.39), 0.93 (0.62 to 1.41), and 1.18 (0.84 to 1.64). Combining CO measurement with genetic susceptibility gave an OR of 0.58 (0.29 to 1.19). Exhaled CO measurement and spirometry were used together in three trials, resulting in the following ORs (95% CI): 0.6 (0.25 to 1.46), 2.45 (0.73 to 8.25), and 3.50 (0.88 to 13.92). Spirometry results alone were used in one other trial with an OR of 1.21 (0.60 to 2.42). Two trials used other motivational feedback measures, with an OR of 0.80 (0.39 to 1.65) for genetic susceptibility to lung cancer alone, and 3.15 (1.06 to 9.31) for ultrasonography of carotid and femoral arteries performed in light smokers (average 10 to 12 cigarettes a day). AUTHORS' CONCLUSIONS: Due to the scarcity of evidence of sufficient quality, we can make no definitive statements about the effectiveness of biomedical risk assessment as an aid for smoking cessation. Current evidence of lower quality does not however support the hypothesis that biomedical risk assessment increases smoking cessation in comparison with standard treatment. Only two studies were similar enough in term of recruitment, setting, and intervention to allow pooling of data and meta-analysis.

Structural basis for autoantibody recognition of phosphatidylserine-beta 2 glycoprotein I and apoptotic cells.

Apoptotic cells contain nuclear autoantigens that may initiate a systemic autoimmune response. To explore the mechanism of antibody binding to apoptotic cells, 3H9, a murine autoantibody with dual specificity for phospholipids and DNA, was used. H chain mutants of 3H9 were constructed, expressed as single-chain Fv (scFv) in Escherichia coli, and assessed for binding to phosphatidylserine, an antigen expressed on apoptotic cells. Both 3H9 and its germline revertant bound to dioleoyl phosphatidylserine in ELISA, and binding was enhanced by beta 2 glycoprotein I (beta 2GPI), a plasma protein that selectively binds to apoptotic cells. Higher relative affinity for DOPS-beta 2GPI was achieved by the introduction of Arg residues into the 3H9 H chain variable region at positions previously shown to mediate DNA binding. Specificity of the two structurally most diverse scFv for apoptotic cells was shown by flow cytometry, and two populations of scFv-bound cells were identified by differences in propidium iodide staining. The results suggest that, in autoimmunity, B cells with Ig receptors for apoptotic cells and DNA are positively selected, and that the antibodies they produce have the potential to affect the clearance and processing of apoptotic cells.

Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells.

Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8(+) T cells express the CD45RA(-)CD62L(-) but lack the CD45RA(+)CD62L(-) T cell effector memory (T(EM)) phenotype. This skewing is not found in CMV- and EBV-specific CD8(+) T cells in HIV-infected individuals. CD95/Fas-induced apoptosis is much higher in the CD45RA(-)CD62L(-) T(EM) cells. However, cytotoxicity and IFNgamma production by HIV-specific CD8(+) T cells is not impaired. Our data suggest that the survival and differentiation of HIV-specific CD8(+) T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells.

Alpha beta TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice.

BACKGROUND: Although the transplantation of solid organs and cellular grafts is a clinical routine, the morbidity and mortality associated with immunosuppression is significant. This could be avoided by the induction of donor-specific tolerance. To develop targeted antirejection strategies and regimens to induce donor-specific tolerance, cell populations in the recipient-mediating rejection of solid organ and cellular grafts must be defined. In this study we examined the role of alpha beta-TCR+ cells in the rejection of allogeneic heart grafts, by use of knockout (KO) mice deficient in the production of alpha beta-TCR+ T cells. METHODS: C57BL/6-TcrbtmlMom (alpha beta-KO) and C57BL6/J (B6) recipient mice were transplanted with B10.BR/SgSnJ (B10.BR) or BALB/c heart allografts. Animals also received bone marrow from normal B10.BR donors, followed by donor-specific or third-party heart transplants. RESULTS: Naive B6 control mice rejected B10.BR and BALB/c grafts within 16 days. In striking contrast, B10.BR and BALB/c heart allografts were indefinitely accepted in unmanipulated alpha beta-KO mice. The immune responsiveness was restored after bone marrow transplantation from normal donors. After bone marrow transplantation major histocompatibility-disparate BALB/c third-party heart grafts were rejected, whereas donor-specific grafts were still accepted. CONCLUSIONS: alpha beta-TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice. Bone marrow chimerism is associated with donor-specific transplantation tolerance.

Clinical applications of mixed chimerism.

Bone marrow transplantation (BMT) is currently a procedure that is associated with high morbidity and mortality. Thus, the clinical application of this technique is limited to the treatment of life-threatening hematopoietic malignancies. The morbidity and mortality of BMT is mainly related to graft-versus-host disease (GVHD), failure of engraftment, and toxicity related to fully myeloablative conditioning. GVHD can be prevented by T-cell depletion. However, T-cell depletion increases the risk of failure of engraftment. With the identification of a facilitating cell population that enables engraftment of hematopoietic stem cells across major histocompatibility barriers, the dichotomy between GVHD and failure of engraftment has been resolved. If one could overcome the toxicity of conditioning with the development of partially ablative conditioning strategies, BMT could be used for the treatment of a variety of nonmalignant diseases, as well as in the induction of donor-specific transplantation tolerance. This review outlines the development and advantages of partially ablative conditioning strategies and illustrates possible applications of the technique. Forty years ago E.D. Thomas discussed the potential of BMT for treating immunodeficiencies and for the induction of transplantation tolerance. BMT can be viewed as a natural form of gene therapy to replace a defective cell or enzyme with a functional and normally regulated one.

Mixed allogeneic chimerism to induce tolerance to solid organ and cellular grafts.

Transplantation of solid organs and cellular grafts has become clinical routine in the last 30 years. However, the requirement for life-long immunosuppression is associated with infections, malignancies and end-organ toxicity. Moreover, the treatment fails to prevent chronic rejection. The induction of donor-specific transplantation tolerance would solve these problems, but has remained an elusive goal. One approach to achieve transplantation tolerance is through hematopoietic chimerism. This review outlines different concepts of hematopoietic chimerism focusing on macrochimerism. Mixed allogeneic chimerism, also known as macrochimerism, is defined as engraftment of hematopoietic stem cells achieved by bone marrow transplantation (BMT). It discusses the advantages and limitations of the BMT as well as approaches to overcome these limitations in the future.

Xenotransplantation: application of disease resistance.

1. Organ transplantation is now clinically routine for patients with end-stage organ failure. One major limitation in transplantation is chronic rejection involving the loss of the graft despite the use of immunosuppressive agents. Haematopoietic stem cell (HSC) chimerism, achieved through bone marrow transplantation (BMT), induces donor-specific tolerance to transplanted organs and prevents chronic rejection. 2. A second major limitation to organ transplantation is the donor shortage. Xenotransplantation, the transplantation of organs between different species, would have the ability to increase the availability of donor organs. 3. Current immunosuppressive therapies do not prevent the rejection of xenografts. Therefore, the only reliable method for achieving donor-specific tolerance to xenografts may require HSC chimerism. 4. In order to justify the use of BMT to induce transplantation tolerance in patients with non-life-threatening diseases, the morbidity and mortality associated with current conditioning regimens must be addressed. 5. The use of partial conditioning regimens to promote engraftment of xenogeneic HSC and the development of donor-specific tolerance may eventually make xenotransplantation in humans a clinical reality. 6. Additional advantages of xenotransplantation are the ability to genetically engineer the donor xenograft and resistance of some xenografts to infection by human viruses because of the species specificity of most viruses. 7. The clinical application of disease resistance for HIV and hepatitis B virus is the focus of the present review.

Unusual case of postoperative infection caused by Morganella morganii.

Morganella morganii is a facultative Gram-negative anaerobe present in the human gastrointestinal system as normal flora. Clinically, the organism is important when it manifests as an opportunistic pathogenic infection elsewhere in the body. This paper reviews an unusual case in which M. morganii is the pathogen responsible for a devastating postoperative infection in a diabetic patient. Currently, there are no known reported cases in the literature of M. morganii as an etiologic pathogen for a postoperative foot infection. Prompt diagnosis and treatment of this organism is imperative to reduce the patient's overall morbidity and mortality.